Laboratorio InmunoBiología Molecular, Hospital General Universitario Gregorio Marañón, Doctor Esquerdo 46, 28007-Madrid, Spain.
Biomaterials. 2012 May;33(15):4002-9. doi: 10.1016/j.biomaterials.2012.02.018. Epub 2012 Feb 27.
We evaluated the 2G-NN16-carbosilane dendrimer activities in Th17 response as a potential therapy for Th17 deregulated pathologies. IL17A, IL17F, IL22, IL23 and other interleukins secreted by Th17 cells CD4+ cells were down regulated when cells were cultured in the presence of this dendrimer. Furthermore, IL17F and IL17A protein levels in splenocytes from mice pretreated with 2G-NN16 dendrimer in a Th17 induction mouse model were lower than those corresponding to PBS treated mice. Treatment of mice with 2G-NN16 inhibited the Th17 response causing much more pathogenicity as indicated by the increase in the number of Candida albicans colonies in the kidneys as compared to PBS-treated mice. All these results suggest a potential pharmacological application for this dendrimer in the therapy of Th17-mediated diseases.
我们评估了 2G-NN16-碳硅烷树枝状大分子在 Th17 反应中的活性,作为治疗 Th17 失调病理的潜在疗法。当细胞在该树枝状大分子存在的情况下培养时,Th17 细胞 CD4+细胞分泌的白细胞介素 17A (IL17A)、白细胞介素 17F (IL17F)、白细胞介素 22 (IL22)、白细胞介素 23 和其他白细胞介素的水平下调。此外,在 Th17 诱导的小鼠模型中,用 2G-NN16 树枝状大分子预处理的小鼠脾细胞中的 IL17F 和 IL17A 蛋白水平低于 PBS 处理的小鼠。与 PBS 处理的小鼠相比,用 2G-NN16 治疗小鼠抑制了 Th17 反应,导致肾脏中白色念珠菌菌落数量增加,表明致病性更高。所有这些结果表明,这种树枝状大分子在 Th17 介导的疾病治疗中有潜在的药理学应用。